Platelet aggregation requires the presence of extracellular fibrinogen and divalent cations. Recently it was shown that platelet stimulation exposes receptors for fibrinogen on the platelet's surface. It has also been suggested that the binding of fibrinogen to these receptors is required for aggregation to occur. The goals of this study are to identify, isolate, and characterize the platelet fibrinogen receptors and to examine the role of divalent cations in fibrinogen binding. Studies in progress are examining the role of endogenous platelet prostaglandin metabolites in the exposure of fibrinogen recptors. In addition, plasmin degradation products of fibrinogen are being purified to examine the structural requirements of fibrinogen for platelet binding. Experiments to identify and isolate the receptor will be based on two techniques. First, platelet-bound fibrinogen will be fixed to the receptor by one of a variety of crosslinking reagents. Second, fibrinogen will be bound to activated Sepharose. Platelet membranes will be isolated and extracted with one of a variety of detergents. The dissolved membrane proteins will then be chromatographed on the Sepharose-fibrinogen to isolate the fibrinogen receptor protein. Finally, the role of the Ca 2 ion in fibrinogen binding will be examined with radioactive Ca 2 ion. The results of these studies should provide important new information regarding the physiology of platelet aggregation. Because platelet aggregation has been implicated in the pathogenesis of atherosclerotic vascular disease, understanding the mechanisms involved in platelet aggregation may prove useful in the design of new specific therapeutic approaches to this disease process.